Salicylate Toxicity PDF

# Introduction - Aspirin is one of the oldest medications that remains a part of current practice - Intentional salicylate overdose usually occurs predominantly in adolescents and young adults. - Overdoses in children are usually accidental & in the elderly they occur as therapeutic misadventures...

# Introduction - Aspirin is one of the oldest medications that remains a part of current practice - Intentional salicylate overdose usually occurs predominantly in adolescents and young adults. - Overdoses in children are usually accidental & in the elderly they occur as therapeutic misadventures. - This is an important problem because delay in treatment of severe intoxication is associated with increased mortality in severe cases. - With good management mortality rates are low but even at best about 5% of severely toxic patients die, usually from cardiovascular & central nervous system complications. # Toxic Dose - Toxic dose = 150 mg/kg - Minimal lethal dose = 450 mg/kg ## Assessing Salicylate Poisoning Dose - Less than 150 mg/kg of aspirin - no symptoms to mild toxicity - Ingestions of 150-300 mg/kg - mild to moderate toxicity - Ingestions of 300-500mg/kg - Serious toxicity - Greater than 500mg/kg - potentially lethal # Pharmacokinetics ## Absorption: - Rapidly absorbed by passive diffusion in the stomach - After absorption ASA is de-acetylated ## Distribution: - 90% bound to albumin in the blood at a dose of 10 mg/dL - An acidic pH promotes the movement of salicylate into the tissues - Has a very short half-life (30 min). - Reach peak levels in 15-60 minutes ## Elimination: - 90% metabolized in the liver, 10% unchanged. - Salicylate is either metabolized to gentisic acid or bound to glycine or glucuronide, or excreted as salicylate - In tubular fluid, nonionized salicylate is reabsorbed. Ionized salicylate cannot be reabsorbed. - Excreted in the urine (PH dependent). # Pathophysiology ## A. CENTRAL NERVOUS SYSTEM - **1) Increased central respiratory drive**: Mechanism of action is unclear. The likely explanation may be the direct stimulation of medullary regulatory activity by salicylic acid. Hyperventilation predominates early in the course of salicylate toxicity resulting in respiratory alkalosis, decreased ionized calcium, and compensatory renal excretion of potassium, sodium, and bicarbonate. - **2) Seizures and coma**: - **Etiology:** As glucose utilization increases, a decrease in brain glucose concentrations may occur producing a relative CNS hypoglycemia despite normal blood glucose concentrations. - Cerebral edema by an, as yet unexplained mechanism - Metabolic acidosis ## B. METABOLIC: - Uncoupling of oxidative phosphorylation leads to a disruption of cellular metabolism due to the interference of the Kreb's cycle and impaired carbohydrate and lipid metabolism. - Substrates are metabolized but the energy produced is dissipated as heat instead of being used to produce adenosine triphosphate (ATP). - The basal metabolic rate increases, placing increased demands on the cardiorespiratory system. - Excess lactic acid results from nonmitochondrial ATP production. # Chronic Salicylism - Most common in the elderly - unintentional - May include any sign consistent with acute toxicity - May also present as: - Delirium - Dementia - Encephalopathy of unknown origin - Congestive heart failure # Table 35-2: Differential Characteristics of Acute and Chronic Salicylate Poisoning | | Acute | Chronic | | ----------- | -------------- | ----------------------------------------------------------------------------------------------------------------------------------------- | | Age | Younger | Older | | Etiology | Overdose usually intentional | Therapeutic misadventures, iatrogenic | | Diagnosis | Easily Recognized | Frequently unrecognized, Underlying disorders (especially chronic pain conditions) | | Other disease states | None | | | Suicidal Ideation | Typical | No | | Clinical Differences | Rapid progression of signs | Acute lung injury (ALI), CNS abnormalities | | Serum Concentrations | Marked elevation | Intermediate elevation | | Mortality | Uncommon when recognized, unless ingestion is massive | Approximately 25% | # Diagnosis ## History: - Amount - Approximate Time Of Ingestion - Possibility Of Long-term Ingestion - Potential Co-ingestants - Approximate Time Of Ingestion - Presence Of Other Medical Conditions (e.g., Cardiac, Renal Disease) ## Physical Exam: - Vital signs. - Cardiovascular, Chest, Abdomen, CNS ## Assessing Salicylate Poisoning from Clinical Evaluation | | Moderate (150-300 mg/kg) | Severe (300-500 mg/kg) | | - | ---------------------------- | -------------------------- | | | Nausea | Delirium | | | Vomiting | Hallucinations | | | Tinnitus | Convulsions | | | Headache | Coma | | | Confusion | Respiratory arrest | | | Hyperventilation | | | | Tachycardia | | | | Fever | | # Diagnosis Continued - Criteria in the 'point of care' setting that can rapidly indicate salicylate poisoning are: - Positive urine ketones - Increase in fatty acid metabolism - **Whole blood glucose and electrolyte determination**: Shows decreased bicarbonate and other electrolyte and glucose abnormalities. - **Whole blood ABG**: Shows characteristic acid-base disturbance of salicylate toxicity. # Management ## EMERGENCY AND SUPPORTIVE MEASURES: - Maintain airway and assist ventilation if necessary. Administer supplemental oxygen and establish intravenous access. - **Fluid resuscitation**: Correction of dehydration with 0.9% sodium chloride or lactated Ringer solution, 10 to 20 mL/kg/h over 1 to 2 hours until a good urine flow is established of at least 2 to 3 mL/kg/h.